5-Item sino-nasal outcome test and 22-item sino-nasal outcome test relationship with endoscopic and radiologic scores in chronic rhinosinusitis with nasal polyps.

BACKGROUND: The 22-item sino-nasal outcome test (SNOT-22) is a frequently used patient-recorded outcome measure in patients with chronic rhinosinusitis with nasal polyps (CRSwNPs). Objective findings of nasal polyps and paranasal sinus inflammation are frequently graded using nasal polyp score (NPS) and Lund-Mackay Score (LMS), respectively. OBJECTIVE: To evaluate a novel, abbreviated, rhinology-focused, five-domain SNOT-5 questionnaire because we had anecdotally noticed a relative disconnect between SNOT-22 and endoscopy and imaging scores. METHODS: We performed a retrospective, cross-sectional, single-center review of patients with CRSwNPs who had filled out a SNOT-22, along with post hoc-derived SNOT-5 scores, which were then assessed in relation to NPS and LMS. RESULTS: A total of 129 patients were included in the analysis. SNOT-5 but not SNOT-22 scores significantly correlated vs either NPS (P < .005) and LMS (P < .001), whereas only SNOT-5 differed significantly when comparing the cohort's lowest and highest tertiles for mean LMS: 11.8 vs 16.8 (95% CI, 1.5-8.4; P < .01) and for mean NPS 12.4 vs 15.6 (95% CI, 0.5-5.9; P < .05). CONCLUSION: In a retrospective, real-life cohort study of CRSwNP, there was a relative disconnect between the significant association of SNOT-5 but not SNOT-22 in relation to objective endoscopy and imaging measures. We, therefore, propose that further prospective intervention studies are indicated in CRSwNP to evaluate the SNOT-5 score including establishing the minimal clinically important difference.

Eosinophil depletion with benralizumab is associated with attenuated mannitol airway hyperresponsiveness in severe uncontrolled eosinophilic asthma.

BACKGROUND: Airway hyperresponsiveness (AHR) and eosinophilia are hallmarks of persistent asthma. OBJECTIVE: We investigated whether eosinophil depletion with benralizumab might attenuate indirect mannitol AHR in severe uncontrolled asthma using a pragmatic open-label design. METHODS: After a 4-week run-in period with provision of usual inhaled corticosteroids and/or long-acting ß-agonist (baseline), adults with mannitol-responsive uncontrolled severe eosinophilic asthma received 3 doses of open-label benralizumab 30 mg every 4 weeks, followed by 16 weeks' washout after the last dose. The primary outcome was doubling difference (DD) in provocative dose of mannitol required to decrease FEV1 by 10% (PD10) at the end point after 12 weeks, powered at 90% with 18 patients required to detect 1 DD. Secondary outcomes included measures assessed by the asthma control questionnaire and mini-asthma quality of life questionnaire. RESULTS: Twenty-one patients completed 12 weeks' benralizumab therapy at the end point at week 12. Mean (SEM) age was 53 (4) years, and FEV1 80.2% (4.1%) inhaled corticosteroid dose was 1895 (59) µg, with 12 receiving long-acting muscarinic antagonist and 13 leukotriene receptor antagonists. Improvement in AHR was significant by 8 weeks, with a mean 2.1 DD (95% confidence interval 1.0, 3.3; P < .01) change in PD10 at week 12, while mean changes in asthma control questionnaire and mini-asthma quality of life questionnaire were significant by week 2 and sustained over 12 weeks, both exceeding the minimal important difference. Peripheral blood eosinophils were depleted by 2 weeks (439 to 6 cells/µL). No significant improvement occurred in lung function after 12 weeks. Domiciliary peak flow and symptoms also improved with benralizumab. CONCLUSION: Eosinophil depletion results in clinically meaningful attenuated AHR in severe uncontrolled asthma patients.

Efficacy of biologic therapy on airway hyperresponsiveness in asthma.

Airway hyperresponsiveness refers to an exaggerated bronchial constrictor response to a given exogenous inhaled agent and is governed by airway smooth muscle along with mucosal inflammation in asthma. In recent years, the advent of biologics and antialarmins has transformed severe asthma treatment in terms of reducing oral-corticosteroid-requiring exacerbations and improving disease control, asthma quality of life, and spirometry-measured lung function. In contrast, there have been comparatively fewer studies investigating the efficacy of biologics in airway hyperresponsiveness. In this focused review, we summarize the existing evidence base in this area regarding omalizumab, mepolizumab, benralizumab, and tezepelumab.

Clinical impact of obesity on oscillometry lung mechanics in adults with asthma.

BACKGROUND: In the year 2035, projections have estimated that 5% of the Scottish population will be morbidly obese defined as a body mass index (BMI) greater than or equal to 40 kg/m2. Airway oscillometry is an effort-independent test akin to bronchial sonar which measures resistance and compliance. OBJECTIVE: To evaluate the impact of obesity on lung mechanics using oscillometry. METHODS: Clinical data for 188 patients with respiratory physician-diagnosed moderate-to-severe asthma were retrospectively collected and analyzed. RESULTS: Obesity (BMI 30-39.9 kg/m2) and morbid obesity (BMI ≥ 40 kg/m2) were associated with a significantly worse heterogeneity of peripheral resistance between 5 Hz and 20 Hz and peripheral compliance as low-frequency reactance at 5 Hz and area under the reactance curve, as compared with normal weight (BMI 18.5-24.9 kg/m2). Cluster analysis incorporating oscillometry identified a patient cohort who was older, obese, and female with combined impairment of spirometry and oscillometry coupled with more frequent severe exacerbations. CONCLUSION: Obesity is associated with worse peripheral airway dysfunction in moderate-to-severe asthma, including a patient cluster who was older, obese, and female with more frequent exacerbations.

Forced Vital Capacity and Low Frequency Reactance Area Measurements Are Associated with Asthma Control and Exacerbations.

INTRODUCTION: Forced vital capacity (FVC) is often preserved in severe asthma unless there is evidence of either airway remodelling or air trapping. Area under the reactance curve (AX) can be used to assess small airways dysfunction related lung stiffness and is related to disease control in severe asthma. METHODS: We explore if there may be a potential synergistic interaction between FVC and AX in terms of impaired asthma control as ACQ and exacerbations requiring oral corticosteroids (OCS). We pragmatically defined < 100% and ≥ 1.0 kPa/L/s as impaired FVC or AX, respectively. RESULTS: Patients with combined impairment of FVC and AX had significantly worse asthma control as higher ACQ, more severe exacerbations requiring OCS and worse spirometry (FEV1 and FEF25-75) than those with impaired FVC but preserved AX. CONCLUSION: This in turn supports using both spirometry and oscillometry to characterise airway physiology more comprehensively in patients with more severe asthma.

Impact of Biologic Therapy on the Small Airways Asthma Phenotype.

The small airways dysfunction (SAD) asthma phenotype is characterised by narrowing of airways < 2 mm in diameter between generations 8 and 23 of the bronchial tree. Recently, this has become particularly relevant as measurements of small airways using airway oscillometry for example, are strong determinants of asthma control and exacerbations in moderate-to-severe asthma. The small airways can be assessed using spirometry as forced expiratory flow rate between 25 and 75% of forced vital capacity (FEF25-75) and has been deemed more accurate in detecting small airways dysfunction than forced expiratory volume in 1 s (FEV1). Oscillometry as the heterogeneity in resistance between 5 and 20 Hz (R5-R20), low frequency reactance at 5 Hz (X5) or area under the reactance curve between 5 Hz and the resonant frequency can also be used to assess the small airways. The small airways can also be assessed using the multiple breath nitrogen washout (MBNW) test giving rise to values including functional residual capacity, lung clearance index and ventilation distribution heterogeneity in the conducting (Scond) and the acinar (Sacin) airways. The ATLANTIS group showed that the prevalence of small airways disease in asthma defined on FEF25-75, oscillometry and MBNW all increased with progressive GINA asthma disease stages. As opposed to topical inhaler therapy that might not adequately penetrate the small airways, it is perhaps more intuitive that systemic anti-inflammatory therapy with biologics targeting downstream cytokines and upstream epithelial anti-alarmins may offer a promising solution to SAD. Here we therefore aim to appraise the available evidence for the effect of anti-IgE, anti-IL5 (Rα), anti-IL4Rα, anti-TSLP and anti-IL33 biologics on small airways disease in patients with severe asthma.

End-point selection to determine the airway-systemic ratio of inhaled corticosteroids in asthma.

The use of adenosine monophosphate challenge and basal cortisol as short-term surrogate end points of airway-systemic effects of inhaled corticosteroids in asthma is not suitable to properly determine the clinically relevant long-term therapeutic index.

Impact of nasal polyps on endotype and phenotype in patients with moderate to severe asthma.

BACKGROUND: Nasal polyps (NPs) are a common comorbidity of asthma. Differences in disease endotype and phenotype may have treatment implications for these concomitant conditions, including biologic therapies. OBJECTIVE: To determine putative differences in type 2 biomarkers, lung function, and asthma control in patients with asthma with NPs (AwNPs) and those with asthma alone (A). METHODS: A total of 140 consecutive patients with moderate to severe asthma with or without endoscopic NPs taking a daily inhaled corticosteroid dose of greater than or equal to 800 µg and at least 1 second-line controller were identified from our National Health Service specialist respiratory and rhinology clinics. Data were collected before starting on biologics, including peripheral blood eosinophils (PBEs), fractional exhaled nitric oxide (FeNO), allergy status, spirometry, impulse oscillometry, Asthma Control Questionnaire, oral corticosteroid requiring asthma exacerbations, NP score, and Lund-Mackay score. RESULTS: The PBE count and FeNO levels were significantly higher (P < .01), whereas specific and total immunoglobulin E levels (P < .05) were significantly lower in AwNPs vs A. In addition, FeNO had sensitivity of 81% and specificity of 67% for detecting NPs (area under the curve = 0.76; P = .001). Patients with AwNPs had less severe asthma than those with asthma without NPs (A), as reflected by fewer exacerbations (P < .001), lower inhaled corticosteroid dose (P < .001), and less impairment of impulse oscillometry (P < .05). CONCLUSION: Patients with moderate to severe asthma with NPs have higher levels of PBE and FeNO despite better asthma control and lower total and specific allergy than those without NPs.